Renal failure is one of the common diseases in human or animals. Diagnosis of renal failure means that more than 75% of kidney loses normally physiological functions, leading to retention of metabolic toxins, disturbance of body fluids, electrolytes and pH, and even to serious systemic complications causing death. Lin (Lin Kai-Wei, “Prognostic Indicators Affecting the Outcome of Acute Renal Failure in Small Animals and Evaluation of Related Infection by Using Central Venous Catheter in Dogs”, Veterinary Medicine Institute of National Chung-Hsing University, master thesis, 2007) reports that renal damage caused by acute renal failure (ARF) is reversible, however the mortality rates of ARF following different treatments (for example, traditional infusion therapy, peritoneal dialysis therapy and hemodialysis therapy) still remain between 30-83%. (Behrend E N, Grauer G F, Mani I, Groman R P, Salman M D, Greco D S, “Hospital-acquired acute renal failure in dogs: 29 cases” (1983-1992), J Am Vet Med Assoc 208: 537-541, 1996; Crisp M S, Chew D J, DiBartola S P, Birchard S J, “Peritoneal dialysis in dogs and cats: 27cases” (1976-1987), J Am Vet Med Assoc 195: 1262-1266, 1989; Forrester S D, McMillan N S, Ward D L, “Retrospective evaluation of acute renal failure in dogs”, J Vet Intern Med 16: 354, 2002.) Also, Lin reports that in the period of from January of 2000 to December of 2006, 1339 dogs and 241 cats received medical treatments due to renal failure in Veterinary Teaching Hospital of National Chung-Hsing University, and the yearly prevalence rate and mortality rate of renal failure are respectively 4-10% and 49-59% in dogs, and 2-10% and 33-62% in cats. In animals determined as suffering acute renal failure (including 501 dogs and 69 cats), the overall yearly morality rate is 81.2% in dogs and 65.2% in cats.
Due to high morality rate of ARF in small animals, the prognostic indications associated with ARF have been intensively investigated to act as early prognostic indication and in turns for selection of appropriate treatment. The prognosis of ARF depends on the cause, severity of renal injury, and accompanying diseases, however literature data in this context are still limited and the results reported are not always consistent.
Current renal failure treatments in small animals include traditional therapy, renal replacement therapy, and diet therapy. Traditional therapy and renal replacement therapy are further described.
1. Transitional Therapy
Traditional therapy for renal failure in small animals mainly includes supportive therapy and infusion therapy (namely, vascular fluid infusion), in combination with medication if necessary, for the correction of body fluids, electrolytes and pH, and reduction of advanced renal damage. Traditional therapy for renal failure are mainly focused on the treatment of reversible renal failure where kidney is temporarily injured or the kidney index is temporarily increased due to other factors and can be resumed after treatment. Irreversible renal failure generally progresses to more severe conditions leading to kidney diseases and even to death. If the kidney index such as BUN (blood urea nitrogen) and CRE (creatinine) becomes worse, the veterinarian will announce euthanasia or advise peritoneal dialysis or hemodialysis therapy, however sometimes the pet still can not recover from renal failure and even die after peritoneal dialysis and hemodialysis therapy.
2. Renal Replacement Therapy
Renal replacement therapy refers to the treatment of temporary substitution for kidney functions in order to restore normal kidney functions, including peritoneal dialysis, hemodialysis, and even kidney transplants and the likes. ARF is one of indications of peritoneal dialysis or hemodialysis in dogs and cats. Traditionally, the response from supportive therapy (i.e., vascular fluid infusion) for 3 to 4 weeks is a criterion to determine whether the pet can recover from renal failure. Specifically, if a pet's health can not be restored from renal failure after supportive therapy and/or fluid infusion therapy, the pet will be requested for dialysis therapy. The pet with renal failure may survive for additional several months via intervention of dialysis therapy. When animals suffer severe oligouria or even anuria, and traditional therapies (supportive therapy and/or fluid infusion therapy) are ineffective to improve azotemia and correct body fluids, electrolytes and pH, a dialysis therapy (peritoneal dialysis or hemodialysis) must be conducted immediately. (Cowgill L D, Elliott D A. Hemodialysis. In: DiBartola S P, ed. “Fluid Therapy in Small Animal Practice”, 2th ed. W.B. Saunder Co., Philadelphia, USA, 1615-1633, 2000; Whittemore J C, Webb C B. “Beyond Fluid Therapy: Treating Acute Renal Failure”, CompCont Ed Pract Vet, 27: 288-297, 2005) Hemodialysis is technically feasible in the treatment of severe uremia, however it is not very common in consideration of availability and economy (about 160,000 NT dollars per week, with uncertain results in the continuous treatment). Peritoneal dialysis and hemodialysis will be described respectively.
A. Peritoneal Dialysis (PD)
Principle and Method:
Peritoneal dialysis is the method of implanting a permanent dialysis catheter into body for direct infusion of a dialysis solution containing electrolytes and glucose in an approximate physiological concentration into abdominal cavity, thereby small molecules (such as uremia waste) and ions in plasma can be exchanged with the dialysis solution through peritoneum acting as dialysis film by diffusion, convention or microfiltration, to correct disturbed electrolytes and body fluids.
Contraindications and Indications:
Peritoneal dialysis is mainly dependent on peritoneum as a dialysis film for substance exchange, thus any conditions which impede the exchange of dialysis solution will retard the feasibility of peritoneal dialysis, for example abdominal wall damage or peritoneal infection leading to the loss of the peritoneal exchange area of more than 50%. The contraindications of peritoneal dialysis in animals may include severe hypoalbuminemia or conditions which may interfere with implantation of peritoneal dialysis catheter, such as severe ascites, recently received abdominal surgery, abdominal mass or intestinal dilation and the likes. In addition, after long-term dialysis, peritoneum may become fibrillated, resulting in deterioration and inefficiency of peritoneal dialysis.
Problems and Complications:
Peritoneal dialysis is technically simple but highly possibly causes complications, thereby its common use is limited. Common complications of peritoneal dialysis include hypoalbuminemia and other problems such as the retention of dialysate, obstruction of dialysis catheter and peritonitis, thus the overall survival rate is only 22% (Crisp M S, Chew D J, DiBartola S P, Birchard S J. “Peritoneal Dialysis in Dogs and Cats: 27 Cases” (1976-1987), J. Am. Vet. Med. Assoc., 195: 1262-1266, 1989). In addition, Beckel et. al. (Beckel N F, Toole T E, Rozanski E A, Labato M A. “Peritoneal Dialysis in the Management of Acute Renal Failure in 5 Dogs with Leptospirosis”, J. Vet. Emerg. Crit. Care, 15:201-205, 2005) reports that peritoneal dialysis in 6 dogs with Leptospirosis shows that the subjects of about 60% take place complications including hypokalemia.
B. Hemodialysis (HD)
Principles and Methods:
Hemodialysis is in principle similar to peritoneal dialysis, however dialysis catheter (hemodialyzer) is the place where solutes are exchanged instead of peritoneum. Its methodology comprises direct exchange of blood with the dialysis solution by extracorporeal circulation, and in order to prevent the solutes from balance during hemodialysis, the blood and dialysis solution shall be continuously refreshed to maintain a concentration gradient thereby to reach a maximum diffusion.
Timing and Indications:
The indications of hemodialysis in dogs and cats mainly are ARF and its complications, acute poisoning and excessive body fluids and so on. In addition, hemodialysis is useful for acute rejection after kidney transplant until the critical conditions are eliminated.
Complications:
Hemodialysis is a technically complicated process and can be applied to physiologically and metabolically disordered patients. Common complications include catheter malfunction or catheter-related infection, low blood pressure, neurologic complications, respiratory complications, panleukopenia and thrombocytopenia, anemia, and amino acid loss. In addition, due to the complexity of the dialysis process per se and the complications of renal failure, the complications of hemodialysis adversely affect various outside kidney systems, therefore it is not easy to determine whether the adverse effects are caused by dialysis therapy itself or uremia, however the frequency and intensity of those adverse effects are generally decreased when the animals are adapted to dialysis or the uremic clearance is under control. (Cowgill L D, Langston C E. “Role of Hemodialysis in the Management of Dogs and Cats with Renal Failure”, Vet. Clin North. Am. Small Anim. Pract., 26: 1347-1378, 1996)
The mortality rate of traditional therapies for renal failure in pets are still high, and the efficiency and cost of peritoneal dialysis and/or hemodialysis therapy still need to be improved, thus there still needs a new treatment for renal failure in pets.